tbuckley/cabot-search huggingface dataset:
Analysis of Stimulant Prescriptions and Drug-Related Poisoning Risk Among Persons Receiving Buprenorphine Treatment for Opioid Use Disorder
Authors: Carrie M. Mintz, Kevin Y. Xu, Ned J. Presnall, Sarah M. Hartz, Frances R. Levin, Jeffrey F. Scherrer, Laura J. Bierut, Richard A. Grucza
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Stimulant medication use is common among individuals receiving buprenorphine for opioid use disorder (OUD). Associations between prescription stimulant use and treatment outcomes in this population have been understudied. <h3>Objectives</h3> To investigate whether use of prescription stimulants was associated with (1) drug-related poisoning and (2) buprenorphine treatment retention. <h3>Design, Setting, and Participants</h3> This retrospective, recurrent-event cohort study with a case-crossover design used a secondary analysis of administrative claims data from IBM MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Primary analyses were conducted from March 1 through August 31, 2021. Individuals aged 12 to 64 years with an OUD diagnosis and prescribed buprenorphine who experienced at least 1 drug-related poisoning were included in the analysis. Unit of observation was the person-day. <h3>Exposures</h3> Days of active stimulant prescriptions. <h3>Main Outcomes and Measures</h3> Primary outcomes were drug-related poisoning and buprenorphine treatment retention. Drug-related poisonings were defined using<i>International Classification of Diseases, Ninth Revision</i>, and<i>International Statistical Classification of Diseases and Related Health Problems, Tenth Revision</i>, codes; treatment retention was defined by continuous treatment claims until a 45-day gap was observed. <h3>Results</h3> There were 13 778 567 person-days of observation time among 22 946 individuals (mean [SD] age, 32.8 [11.8] years; 50.3% men) who experienced a drug-related poisoning. Stimulant treatment days were associated with 19% increased odds of drug-related poisoning (odds ratio [OR], 1.19 [95% CI, 1.06-1.34]) compared with nontreatment days; buprenorphine treatment days were associated with 38% decreased odds of poisoning (OR, 0.62 [95% CI, 0.59-0.65]). There were no significant interaction effects between use of stimulants and buprenorphine. Stimulant treatment days were associated with decreased odds of attrition from buprenorphine treatment (OR, 0.64 [95% CI, 0.59-0.70]), indicating that stimulants were associated with 36% longer mean exposure to buprenorphine and its concomitant protection. <h3>Conclusions and Relevance</h3> Among persons with OUD, use of prescription stimulants was associated with a modest increase in per-day risk of drug-related poisoning, but this risk was offset by the association between stimulant use and improved retention to buprenorphine treatment, which is associated with protection against overdose.
Tissue-resident memory T cells from a metastatic vaginal melanoma patient are tumor-responsive T cells and increase after anti-PD-1 treatment
Authors: Angela Pizzolla, Simon Paul Keam, Ismael A Vergara, Franco Caramia, Niko Thio, Minyu Wang, Nikolce Kocovski, Daniela Tantalo, Jafar Jabbari, George Au-Yeung, Shahneen Sandhu, David E Gyorki, Alison Weppler, Maurizio Perdicchio, Grant A McArthur, Anthony T Papenfuss, Paul Joseph Neeson
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Vaginal melanoma (VM) is a rare cancer and has a poor response to immune checkpoint blockade (ICB). CD8 + Tissue Resident Memory (TRM) T cells proliferate in response to ICB and correlate with longer survival in metastatic cutaneous melanoma. However, their capacity to respond to VM and their neoantigens is not known. Methods Using longitudinal samples, we explored the evolution of VM mutations by whole-exome sequencing and RNAseq, we also defined the immune context using multiplex immunohistochemistry and nanostring pan cancer immune profile. Then using fresh single cell suspensions of the metastatic samples, we explored VM T cells via mass cytometry and single cell RNAseq and T cell receptor sequencing (TCRseq). Finally, we investigated TRM, pre-TRM and exhausted T cell function against melanoma neo-antigens and melanoma differentiation antigens in vitro. Results Primary VM was non-inflamed and devoid of CD8 + TRM cells. In contrast, both metastases showed proliferating CD8 + TRM were clustered at the tumor margin, with increased numbers in the second ICB-refractory metastasis. The first metastasis showed dense infiltration of CD8 + T cells, the second showed immune exclusion with loss of melanoma cell Major histocompatibility complex (MHC)-I expression associated with downregulation of antigen presentation pathway gene expression. CD8 + TRM from both metastases responded to autologous melanoma cells more robustly than all other CD8 + T cell subsets. In addition, CD8 + TRM shared TCR clones across metastases, suggesting a response to common antigens, which was supported by recognition of the same neoantigen by expanded tumor infiltrating lymphocytes. Conclusions In this study, we identified TRM clusters in VM metastases from a patient, but not primary disease. We showed TRM location at the tumor margin, and their superior functional response to autologous tumor cells, predicted neoantigens and melanoma differentiation antigens. These CD8 + TRM exhibited the highest tumor-responsive potential and shared their TCR with tumor-infiltrating effector memory T cells. This suggests VM metastases from this patient retain strong antitumor T cell functional responses; however, this response is suppressed in vivo. The loss of VG MHC-I expression is a common immune escape mechanism which was not addressed by anti-PD-1 monotherapy; rather an additional targeted approach to upregulate MHC-I expression is required.
Trends in Cancer Mortality Among Black Individuals in the US From 1999 to 2019
Authors: Wayne R. Lawrence, Jennifer K. McGee-Avila, Jacqueline B. Vo, Qianlai Luo, Yingxi Chen, Maki Inoue-Choi, Amy Berrington de González, Neal D. Freedman, Meredith S. Shiels
Journal: JAMA Oncology (2022)

Cancer is the second leading cause of mortality in the US. Despite national decreases in cancer mortality, Black individuals continue to have the highest cancer death rates.To examine national trends in cancer mortality from 1999 to 2019 among Black individuals by demographic characteristics and to compare cancer death rates in 2019 among Black individuals with rates in other racial and ethnic groups.This serial cross-sectional study used US national death certificate data obtained from the National Center for Health Statistics and included all cancer deaths among individuals aged 20 years or older from January 1999 to December 2019. Data were analyzed from June 2021 to January 2022.Age, sex, and race and ethnicity.Trends in age-standardized mortality rates and average annual percent change (AAPC) in rates were estimated by cancer type, age, sex, and race and ethnicity.From 1999 to 2019, 1 361 663 million deaths from cancer occurred among Black individuals. The overall cancer death rate significantly decreased among Black men (AAPC, -2.6%; 95% CI, -2.6% to -2.6%) and women (AAPC, -1.5%; 95% CI, -1.7% to -1.3%). Death rates decreased for most cancer types, with the greatest decreases observed for lung cancer among men (AAPC, -3.8%; 95% CI, -4.0% to -3.6%) and stomach cancer among women (AAPC, -3.4%; 95% CI, -3.6% to -3.2%). Lung cancer mortality also had the largest absolute decreases among men (-78.5 per 100 000 population) and women (-19.5 per 100 000 population). We observed a significant increase in deaths from liver cancer among men (AAPC, 3.8%; 95% CI, 3.0%-4.6%) and women (AAPC, 1.8%; 95% CI, 1.2%-2.3%) aged 65 to 79 years. There was also an increasing trend in uterus cancer mortality among women aged 35 to 49 years (2.9%; 95% CI, 2.3% to 2.6%), 50 to 64 years (2.3%; 95% CI, 2.0% to 2.6%), and 65 to 79 years (1.6%; 95% CI, 1.2% to 2.0%). In 2019, Black men and women had the highest cancer mortality rates compared with non-Hispanic American Indian/Alaska Native, Asian or Pacific Islander, and White individuals and Hispanic/Latino individuals.In this cross-sectional study, there were substantial decreases in cancer death rates among Black individuals from 1999 to 2019, but higher cancer death rates among Black men and women compared with other racial and ethnic groups persisted in 2019. Targeted interventions appear to be needed to eliminate social inequalities that contribute to Black individuals having higher cancer mortality.
Comparison of biochemical, microbial and mucosal mRNA expression in bile acid diarrhoea and irritable bowel syndrome with diarrhoea
Authors: Michael Camilleri, Paula Carlson, Joelle BouSaba, Sanna McKinzie, Priya Vijayvargiya, Yorick Magnus, Wassel Sannaa, Xiao Jing Wang, Victor Chedid, Ting Zheng, Daniel Maselli, Jessica Atieh, Ann Taylor, Asha A Nair, Nagaswaroop Kengunte Nagaraj, Stephen Johnson, Jun Chen, Duane Burton, Irene Busciglio
Journal: Gut (2022)

There are altered mucosal functions in irritable bowel syndrome with diarrhoea (IBS-D); ~30% of patients with IBS-D have abnormal bile acid (BA) metabolism (ABAM) and diarrhoea (summarised as BAD).
Oral antimicrobial peptide-EGCG nanomedicines for synergistic treatment of ulcerative colitis
Authors: Shengsheng Liu, Yingui Cao, Lingli Ma, Jianfeng Sun, Lorenzo Ramos-Mucci, Ya Ma, Xiao Yang, Zhenhua Zhu, Jianxiang Zhang, Bo Xiao
Journal: Journal of Controlled Release (2022)
Planning for progress: A US regulatory approach to advancing the clinical development of gene therapies
Authors: Mantej Chhina, Daniela Drago, Adora Ndu
Journal: Molecular Therapy (2022)

While the gene-therapy field has experienced tremendous scientific, technological, and regulatory advances, understanding the factors that are slowing the rate of development and approval is important to ensure that barriers are addressed. 1 Marks P. Enhancing gene therapy regulatory interactions [published online ahead of print, 2022 Apr 3]. Expert Opin. Biol. Ther. 2022; : 1-2https://doi.org/10.1080/14712598.2022.2060736 Crossref PubMed Scopus (3) Google Scholar This article reflects on progress made under the Regenerative Medicine Advanced Therapy (RMAT) designation program, discusses barriers to efficient clinical development of gene-therapy products, and opines on the role of PDUFA VII as a key driver in facilitating efficient development of, and access to, gene therapies in the United States.
The logic of challenging research into bias and social disparity
Authors: Regina Rini
Journal: Behavioral and Brain Sciences (2022)

Abstract There are two problems with the logic of Cesario's argument for abandoning existing research on social bias. First, laboratory findings of decisional bias have social significance even if Cesario is right that the research strips away real-world context. Second, the argument makes overly skeptical demands of a research program seeking complex causal linkages between micro- and macro-scale phenomena.
Abstract A001: Modeling cancer’s ecological and evolutionary dynamics
Authors: Anuraag Bukkuri, Kenneth J. Pienta, Ian Hockett, Robert H. Austin, Emma U. Hammarlund, Sarah R. Amend, Joel S. Brown
Journal: Cancer Research (2022)

Abstract We present a theoretical modeling framework, called the G function, to understand cancer speciation, diversification, and environmental adaptation. The G function integrates both the ecology and evolution of cancer and has been used in evolutionary ecology. However, the G function has not yet been widely applied to problems in cancer. Here, we build the G-function framework from fundamental Darwinian principles and discuss how cancer is inherently an evolutionary game. We begin with a simple model of cancer growth and add on components of cancer cell competition and drug resistance. To aid in exploration of eco-evolutionary modeling with this approach, we also present a user-friendly online tool. We argue that G-functions are useful to understand the games cancer plays in a biologically mechanistic fashion. Citation Format: Anuraag Bukkuri, Kenneth J. Pienta, Ian Hockett, Robert H. Austin, Emma U. Hammarlund, Sarah R. Amend, Joel S. Brown. Modeling cancer’s ecological and evolutionary dynamics [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A001.
An Autologous Dendritic Cell Vaccine Promotes Anticancer Immunity in Patients with Ovarian Cancer with Low Mutational Burden and Cold Tumors
Authors: Jitka Fucikova, Michal Hensler, Lenka Kasikova, Tereza Lanickova, Josef Pasulka, Jana Rakova, Jana Drozenova, Tessa Fredriksen, Marek Hraska, Tereza Hrnciarova, Klara Sochorova, Daniela Rozkova, Ludek Sojka, Pavel Dundr, Jan Laco, Tomas Brtnicky, Ivan Praznovec, Michael J. Halaska, Lukas Rob, Ales Ryska, An Coosemans, Ignace Vergote, David Cibula, Jirina Bartunkova, Jérôme Galon, Lorenzo Galluzzi, Radek Spisek
Journal: Clinical Cancer Research (2022)

The successful implementation of immune checkpoint inhibitors (ICI) in the clinical management of various solid tumors has raised considerable expectations for patients with epithelial ovarian carcinoma (EOC). However, EOC is poorly responsive to ICIs due to immunologic features including limited tumor mutational burden (TMB) and poor lymphocytic infiltration. An autologous dendritic cell (DC)-based vaccine (DCVAC) has recently been shown to be safe and to significantly improve progression-free survival (PFS) in a randomized phase II clinical trial enrolling patients with EOC (SOV01, NCT02107937).We harnessed sequencing, flow cytometry, multispectral immunofluorescence microscopy, and IHC to analyze (pretreatment) tumor and (pretreatment and posttreatment) peripheral blood samples from 82 patients enrolled in SOV01, with the aim of identifying immunologic biomarkers that would improve the clinical management of patients with EOC treated with DCVAC.Although higher-than-median TMB and abundant CD8+ T-cell infiltration were associated with superior clinical benefits in patients with EOC receiving standard-of-care chemotherapy, the same did not hold true in women receiving DCVAC. Conversely, superior clinical responses to DCVAC were observed in patients with lower-than-median TMB and scarce CD8+ T-cell infiltration. Such responses were accompanied by signs of improved effector functions and tumor-specific cytotoxicity in the peripheral blood.Our findings suggest that while patients with highly infiltrated, "hot" EOCs benefit from chemotherapy, women with "cold" EOCs may instead require DC-based vaccination to jumpstart clinically relevant anticancer immune responses.
Review of 2022 WHO guidelines on the control and elimination of schistosomiasis
Authors: Nathan C Lo, Fernando Schemelzer Moraes Bezerra, Daniel G Colley, Fiona M Fleming, Mamoun Homeida, Narcis Kabatereine, Fatma M Kabole, Charles H King, Margaret A Mafe, Nicholas Midzi, Francisca Mutapi, Joseph R Mwanga, Reda M R Ramzy, Fadjar Satrija, J Russell Stothard, Mamadou Souncalo Traoré, Joanne P Webster, Jürg Utzinger, Xiao-Nong Zhou, Anthony Danso-Appiah, Paolo Eusebi, Eric S Loker, Charles O Obonyo, Reginald Quansah, Song Liang, Michel Vaillant, M Hassan Murad, Paul Hagan, Amadou Garba
Journal: The Lancet Infectious Diseases (2022)
Abstract B034: Targeting cellular plasticity-driven metabolic adaptation to overcome chemoresistance in GBM
Authors: Atique U. Ahmed, Jack M. Shireman, Fatemeh Atash, Gina Lee, Eunus S. Ali, Miranda R. Saathoff, Cheol H. Park, Sol Savchuk, Shivani Baisiwala, Jason Miska, Maciej S. Lesniak, C. David James, Roger Stupp, Priya Kumthekar, Craig M. Horbinski, Issam Ben-Sahra
Journal: Cancer Research (2022)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR011) of the Conference Proceedings. Citation Format: Atique U. Ahmed, Jack M. Shireman, Fatemeh Atash, Gina Lee, Eunus S. Ali, Miranda R. Saathoff, Cheol H. Park, Sol Savchuk, Shivani Baisiwala, Jason Miska, Maciej S. Lesniak, C. David James, Roger Stupp, Priya Kumthekar, Craig M. Horbinski, Issam Ben-Sahra. Targeting cellular plasticity-driven metabolic adaptation to overcome chemoresistance in GBM [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B034.
Device-assisted submucosal tunneling endoscopic resection for rectal gastrointestinal stromal tumor
Authors: Marina Kim, Rodrigo Duarte-Chavez, Michel Kahaleh
Journal: Endoscopy (2022)

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, although rare in the rectum. GISTs range from tumors with benign behavior to aggressive sarcomas [1] [2]. Resection is recommended for localized tumors larger than 2 cm [3]. The surgical treatment for rectal GIST is not standardized; conventional surgery is difficult in the rectum since the pelvis is deep, narrow, and in close proximity of other organs, so less invasive modalities that can provide R0 en bloc resection are attractive [2] [4].
Demographic and Clinical Factors Associated With Anti–SARS-CoV-2 Antibody Levels After 2 BNT162b2 mRNA Vaccine Doses
Authors: Su Youn Nam, Seong Woo Jeon, Hyun Seok Lee, Hee Jeong Lim, Dong Wook Lee, Seung Soo Yoo
Journal: JAMA Network Open (2022)

The factors associated with long-term serum levels of anti-SARS-CoV-2 antibodies after COVID-19 vaccination in healthy individuals have rarely been investigated.To investigate factors associated with anti-SARS-CoV-2 antibody levels.This prospective cohort study included health care workers at Kyungpook National University Chilgok Hospital (Daegu, Korea) with no history of SARS-CoV-2 infection who received 2 doses of the BNT162b2 mRNA COVID-19 vaccine (Pfizer/BioNTech; first dose, March 17-20, 2021; second dose, April 7-10, 2021). Serum samples were collected at 2, 4, and 6 months after the second injection.SARS-CoV-2 BNT162b2 mRNA vaccine.Anti-SARS-CoV-2 specific antibodies were measured using enzyme-linked immunosorbent assay kits up to 6 months after the receipt of 2 doses of the BNT162b2 mRNA COVID-19 vaccine. The main outcome was factors associated with anti-SARS-CoV-2 antibody levels at 6 months.All 50 participants (mean [SD] age, 34.7 [9.4] years; 10 [20.0%] male; mean [SD] body mass index, 21.8 [5.4]) acquired anti-SARS-CoV-2 antibodies and maintained positive antibody (cutoff ≥30%) up to 6 months. The mean serum antibody level decreased with time (91.9%, 89.3%, and 81.5% at 2, 4, and 6 months, respectively). Serum antibody levels at 6 months were correlated with antibody levels at 2 months (R = 0.944; P < .001). The anti-SARS-CoV-2-specific antibody level was inversely correlated with weight, body mass index, body fat amount, and body weight to height ratio in Spearman correlation analysis. A 1-SD increase in body weight, weight to height ratio, and body mass index was associated with a 4%- to 5%-decrease in anti-SARS-CoV-2 antibodies in multiple linear regression analysis for women. In multivariate analysis for categorized variables, lower serum level of antibody (ie, <81.5%) was associated with weight (weight ≥55 kg: odds ratio, 9.01; 95% CI, 1.44-56.40). The probabilities of less than 70% and less than 80% antibody at 6 months were 0% and 11% in participants weighing less than 55 kg, respectively, but 16% and 42% in participants weighing 55 kg or greater.In this study, the inverse correlation of anti-SARS-CoV-2-specific antibody levels with weight was sustained up to 6 months after vaccination. A booster shot of BNT162b2 mRNA vaccination may be given later than 6 months after the second dose in young and middle-aged healthy persons with low body weight.
Gas Exchange and Respiratory Mechanics after a Cardiac Arrest: A Clinical Description of Cardiopulmonary Resuscitation–associated Lung Edema
Authors: François M. Beloncle, Hamid Merdji, Arnaud Lesimple, Bertrand Pavlovsky, Elise Yvin, Dominique Savary, Alain Mercat, Ferhat Meziani, Jean-Christophe Richard
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Gas Exchange and Respiratory Mechanics after a Cardiac Arrest: A Clinical Description of Cardiopulmonary Resuscitation–associated Lung Edema." American Journal of Respiratory and Critical Care Medicine, 206(5), pp. 637–640
Muscle Protein Synthesis after Protein Administration in Critical Illness
Authors: Lee-anne S. Chapple, Imre W. K. Kouw, Matthew J. Summers, Luke M. Weinel, Samuel Gluck, Eamon Raith, Peter Slobodian, Stijn Soenen, Adam M. Deane, Luc J. C. van Loon, Marianne J. Chapman
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Dietary protein may attenuate the muscle atrophy experienced by patients in the ICU, yet protein handling is poorly understood. Objectives: To quantify protein digestion and amino acid absorption and fasting and postprandial myofibrillar protein synthesis during critical illness. Methods: Fifteen mechanically ventilated adults (12 male; aged 50 ± 17 yr; body mass index, 27 ± 5 kg⋅m−2) and 10 healthy control subjects (6 male; 54 ± 23 yr; body mass index, 27 ± 4 kg⋅m−2) received a primed intravenous L-[ring-2H5]-phenylalanine, L-[3,5-2H2]-tyrosine, and L-[1-13C]-leucine infusion over 9.5 hours and a duodenal bolus of intrinsically labeled (L-[1-13C]-phenylalanine and L-[1-13C]-leucine) intact milk protein (20 g protein) over 60 minutes. Arterial blood and muscle samples were taken at baseline (fasting) and for 6 hours following duodenal protein administration. Data are mean ± SD, analyzed with two-way repeated measures ANOVA and independent samples t test. Measurements and Main Results: Fasting myofibrillar protein synthesis rates did not differ between ICU patients and healthy control subjects (0.023 ± 0.013% h−1 vs. 0.034 ± 0.016% h−1; P = 0.077). After protein administration, plasma amino acid availability did not differ between groups (ICU patients, 54.2 ± 9.1%, vs. healthy control subjects, 61.8 ± 13.1%; P = 0.12), and myofibrillar protein synthesis rates increased in both groups (0.028 ± 0.010% h−1 vs. 0.043 ± 0.018% h−1; main time effect P = 0.046; P-interaction = 0.584) with lower rates in ICU patients than in healthy control subjects (main group effect P = 0.001). Incorporation of protein-derived phenylalanine into myofibrillar protein was ∼60% lower in ICU patients (0.007 ± 0.007 mol percent excess vs. 0.017 ± 0.009 mol percent excess; P = 0.007). Conclusions: The capacity for critically ill patients to use ingested protein for muscle protein synthesis is markedly blunted despite relatively normal protein digestion and amino acid absorption.
The WHO Hub for Pandemic and Epidemic Intelligence; supporting better preparedness for future health emergencies
Authors: Oliver Morgan, Richard Pebody
Journal: Eurosurveillance (2022)

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